The development of rapid detection tools for viruses is vital for the prevention of pandemics and biothreats. Aptamers that target inactivated viruses are attractive for sensors due to their improved biosafety. Here, we evaluated a DNA aptamer (named as 6.
View Article and Find Full Text PDFTripartite motif (TRIM)-containing proteins, one of the largest subfamilies of the RING type E3 ubiquitin ligases, control important biological processes such as cell apoptosis, autophagy, signal transduction, innate immunity and tumorigenesis. So far, the mutual regulation between TRIM family members has rarely been reported. Here, we found for the first time that there was a direct mutual regulation between TRIM21 and TRIM8 in lung and renal cancer cells, mechanistically by activating their proteasome pathway via Lys48 (K48)- linked ubiquitination.
View Article and Find Full Text PDFSmall molecule-binding aptamers often suffer from high cross reactivity to structure analogues in biological samples, limiting their value for clinical diagnosis. Herein, we present a method to overcome this issue, by performing binding-inhibited organic reaction-based regioselective selection of aptamers against homocysteine (Hcy), which is a marker for diagnosing many disorders including stroke and Alzheimer's. This approach has led to isolation of a DNA aptamer that binds to the alkane thiol chain of Hcy with exceptional specificity against cysteine.
View Article and Find Full Text PDFArgonaute proteins, which consist of AGO1, AGO2, AGO3 and AGO4, are key players in microRNA-mediated gene silencing. So far, few non-microRNA related biological roles of AGO4 have been reported. Here, we first found that AGO4 had low expression in non-small cell lung cancer (NSCLC) patient tumor tissues and could suppress NSCLC cell proliferation and metastasis.
View Article and Find Full Text PDFTumor necrosis factor alpha (TNF-α) is a critical pro-inflammatory cytokine in a wide range of tumors and infectious diseases. This study showed for the first time that TNF-α could specifically bind to certain intracellular or circulating inflammation-related microRNAs both in vitro and in vivo. The binding sites of TNF-α to microRNAs are located at the N-terminal of TNF-α and the 3'-GGUU motif of microRNAs.
View Article and Find Full Text PDFIn this study, the CAR-like multivalent aptamer nanoparticles (X-polymers) were assembled with the dimer of murine CD28 RNA aptamer (CD28Apt7), the tetramer of CTLA-4 (cytotoxic T-lymphocyte-associated protein 4) RNA aptamer (Del60), and a folic acid labeled ssDNA fragment in a stable nucleic acid three-way junction scaffold (3WJ). Results showed that the X-polymers could recognize both the mCD28 and mCTLA-4 molecules. Confocal imaging and flow cytometry assays showed that the X-polymers could target both T cells and B16 cells .
View Article and Find Full Text PDFThe heterogeneous nuclear ribonucleoprotein A1 (hnRNP A1) was reported to participate in the development of a variety of tumors. BC15 is a DNA aptamer targeting hnRNP A1. Firstly, through sequence truncation, we identified 31-mer sequence BC15-31 as the core sequence of BC15 with a strong binding affinity and high selectivity to the hnRNP A1 protein.
View Article and Find Full Text PDFHuman vasorin (VASN) as a type I transmembrane protein, is a potential biomarker of hepatocellular carcinoma, which could expedite HepG2 cell proliferation and migration significantly . The ectodomain of VASN was proteolytically released to generate soluble VASN (sVASN), which was validated to be the active form. Among several monoclonal antibodies produced against sVASN, the clone V21 was found to bind with the recombinant human sVASN (rhsVASN) with the highest affinity and specificity, and also have inhibitory effects on proliferation and migration of HepG2 cells.
View Article and Find Full Text PDFThe type A influenza viruses are the most virulent and variable human pathogens with epidemic or even pandemic threat. The development of sensitive, specific and safe field testing methods is in particular need and quite challenging. We report here the selection and practical utilization of the inactivated influenza virus-specific aptamers.
View Article and Find Full Text PDFACS Appl Mater Interfaces
January 2018
Surface plasmon resonance and quartz crystal microbalance are workhorses of protein-DNA interaction research for over 20 years, providing ways to quantitatively determine the protein-DNA binding. However, the cost, necessary technical expertise, and severe nonspecific adsorption poses barriers to their use. Convenient and effective techniques for the measurement of protein-DNA binding affinity and the epitope binning between DNA and proteins for developing highly sensitive detection platform remain challenging.
View Article and Find Full Text PDFGADD45A (growth arrest and DNA damage inducible alpha), a stress response gene induced by genotoxic and nongenotoxic stresses, is implicated in various key processes, including the control of cell cycle checkpoints and DNA repair. The expression of GADD45A is directly regulated by numerous transcription factors, with p53 being the most representative. Moreover, post-transcriptional regulation also plays a role in GADD45A expression.
View Article and Find Full Text PDFObjective: To investigate the changes in the expression level of sRNA SpR19 and its potential target protein GroEL in clinical isolates of Streptococcus mutans with different cariogenicity exposed to different pH conditions and explore the possibility of using these molecules as biomarkers for assessing the cariogenicity of the bacteria.
Methods: The total RNAs were extracted from the clinical isolates of Streptococcus mutans with high (strain 17) and low cariogenicity (strain 5) for high-throughput sequencing for profiling of the differentially expressed sRNAs. The candidate sRNA, SpR19, was selected for further study on the basis of bioinformatics analysis considering the role of its potential target in the cariogenic process.
Both tumor and adjacent normal tissues are valuable in cancer research. Transcriptional response profiles represent the changes of gene expression levels between paired tumor and adjacent normal tissues. In this study, we performed a pan-cancer analysis based on the transcriptional response profiles from 633 samples across 13 cancer types.
View Article and Find Full Text PDFThis study investigated the effects of altered CXCL12/CXCR4 axis on the bone morphogenetic protein 2 (BMP-2)/Smad/runt-related transcription factor 2 (Runx2)/Osterix (Osx) signal axis and osteogenic gene expression during osteogenic differentiation of mesenchymal stem cells (MSCs), to gain understanding of the link between migration and osteogenic differentiation signal axis and MSCs osteogenic differentiation mechanisms. The pHBAd-MCMV- CXCL12-GFP vector (Ad-CXCL12) was constructed and quantitative polymerase chain reaction (qPCR)/western blotting used to determine CXCL12 expression in Ad-CXCL12-transfected MSCs. MSCs were treated with Ad-CXCL12 and AMD3100 (CXCL12 inhibitor) to detect BMP-2/Smad/Runx2/Osterix expression, bone sialoprotein (BSP), osteocalcin (OCN) and osteopontin (OPN) mRNA expression, and alkaline phosphatase (ALP) activity.
View Article and Find Full Text PDFBreast cancer is a disease with high heterogeneity. Many issues on tumorigenesis and progression are still elusive. It is critical to identify genes that play important roles in the progression of tumors, especially for tumors with poor prognosis such as basal-like breast cancer and tumors in very young women.
View Article and Find Full Text PDFBackground: Gut microbes play a critical role in human health and disease, and researchers have begun to characterize their genomes, the so-called gut metagenome. Thus far, metagenomics studies have focused on genus- or species-level composition and microbial gene sets, while strain-level composition and single-nucleotide polymorphism (SNP) have been overlooked. The gut metagenomes of type 2 diabetes (T2D) patients have been found to be enriched with butyrate-producing bacteria and sulfate reduction functions.
View Article and Find Full Text PDFProtein-coding genes and non-coding RNAs cooperate mutually in cells. Integrative analysis of protein-coding and non-coding RNAs may facilitate characterizing tumor heterogeneity. We introduced integrated consensus clustering (ICC) method to integrate mRNA, miRNA and lncRNA expression profiles of 431 primary clear cell renal cell carcinomas (ccRCCs).
View Article and Find Full Text PDFThis study proposes a facile method for synthesis of Au-coated magnetic nanoparticles (AuMNPs) core/shell nanocomposites with nanoscale rough surfaces. MnFe2O4 nanoparticles (NPs) were first modified with a uniform polyethylenimine layer (2 nm) through self-assembly under sonication. The negatively charged Au seeds were then adsorbed on the surface of the MnFe2O4 NPs through electrostatic interaction for Au shell formation.
View Article and Find Full Text PDFIn recent years, p53 was identified to regulate the expression of many miRNAs and was also regulated by miRNAs. In this paper, we found that miR-138 showed a pronounced increase after p53 activation in human non-small cell lung cancer (NSCLC) cells, which is mediated by p53 binding sites in the promoter region of its host gene, but this did not happen with rat and mouse cells. More interestingly, we found that p53 could be also regulated by miR-138 in mouse and rat cells, but not in the human NSCLC cells.
View Article and Find Full Text PDFMicroRNAs (miRNAs) suppress targeting gene expression through blocking translation or triggering mRNA degradation and, in general, act in trans, through a partially complementary interaction with the 3' untranslated region (3' UTR) or coding regions of a target gene. Although it has been reported previously that some miRNAs suppress their target genes on the opposite strand with a fully complementary sequence (i.e.
View Article and Find Full Text PDFA magnetically assisted surface-enhanced Raman scattering (SERS) biosensor for single-cell detection of S. aureus on the basis of aptamer recognition is reported for the first time. The biosensor consists of two basic elements including a SERS substrate (Ag-coated magnetic nanoparticles, AgMNPs) and a novel SERS tag (AuNR-DTNB@Ag-DTNB core-shell plasmonic NPs or DTNB-labeled inside-and-outside plasmonic NPs, DioPNPs).
View Article and Find Full Text PDFVasorin (VASN) is a type I transmembrane protein that plays important roles in tumor development and vasculogenesis. In this paper, we showed that VASN could be a key mediator of communication between tumor cells and endothelial cells. We confirmed for the first time that HepG2-derived VASN can be transferred to human umbilical vein endothelial cells (HUVECs) via receptor mediated endocytosis of exosomes, at least in part through HSPGs.
View Article and Find Full Text PDFIn this study, we further investigated a previously developed aptamer targeting ROS 17/2.8 (rat osteosarcoma) cells. We found that this C6-8 aptamer specifically binds to heterogeneous nuclear ribonucleoprotein (hnRNP) A2/B1 and that it specifically labeled multiple tumor-cell lines as effectively as hnRNP A2/B1 monoclonal antibodies.
View Article and Find Full Text PDFUnlabelled: We report a new biomarker of hepatocarcinoma, vasorin (VASN), screened by a subtractive EMSA-SELEX strategy from AFP negative serum of hepatocellular carcinoma (HCC) patients with extrahepatic metastases. VASN was verified to be highly expressed in sera of 100 cases of HCC patients compared with 97 cases of normal persons and 129 cases of hepatitis patients. Further validation by Q-PCR,IFA and Western blot showed higher expression of VASN at mRNA and protein levels in HCC cell lines and HCC tissues than in normal controls.
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